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Full-Text Articles in Cell Biology

Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long Dec 2014

Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long

Theses and Dissertations

Tularemia is a potentially fatally illness caused by the facultative intracellular Gram-negative bacterium Francisella tularensis. Virulent strains of F. tularensis can cause a fatal disease after inhalation of a few as ten organisms. Due to the highly pathogenic features of Francisella, it has been designated as a Tier 1 select agent, meaning that its possession and handling is highly restricted. Macrophages are phagocytes that play a central role in the innate immune response to infection that can be used by certain pathogens, including Francisella, as a niche for bacterial replication and dissemination during infection. After infection of macrophages Francisella escapes ...


Characterization Of Efferosome Maturation And The Processing Of Apoptotic Bodies, Yohan Kim Aug 2014

Characterization Of Efferosome Maturation And The Processing Of Apoptotic Bodies, Yohan Kim

Electronic Thesis and Dissertation Repository

Every day billions of cells in our bodies undergo apoptosis and are cleared through efferocytosis – a phagocytosis-like process in which phagocytes engulf and degrade apoptotic cells. Proper processing of efferosomes prevents inflammation and immunogenic presentation of antigens. In this thesis I determined that the early stages of efferosome maturation parallel that of the pro-immunogenic phagocytosis of pathogens. Mass spectrometry analysis of later maturation stages identified unique regulatory proteins on efferosomes and phagosomes. Keys among these were Rab17 and Rab45 on efferosomes versus Rab6b and PI-4-Kinase on phagosomes. The later would allow for antigen presentation from phagosomes, while the former would ...


Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay Jan 2014

Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay

Publicly Accessible Penn Dissertations

Hypoxia-inducible factors (HIFs) mediate adaptation to low O2, or hypoxia, are important at every stage of tumor initiation, and impact the progression of a variety of diseases, including colorectal cancer. This body of work investigates the role of hypoxia and HIF-mediated signaling in both tumor cells and macrophages across the natural history of inflammation-induced cancers. First, the effect of HIF inhibition in tumor parenchyma and stroma in extant colitis-associated colon carcinomas (CAC) is investigated using acriflavine (ACF), a naturally occurring compound known to repress HIF transcriptional activity. Pharmacologic HIF inhibition represents a novel therapeutic strategy for cancer treatment and data ...


Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler Jan 2014

Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler

Publicly Accessible Penn Dissertations

Hematopoiesis in human bone marrow generates every second about 105 – 106 anucleated platelets and red blood cells as well as nucleated white blood cells that are capable of infiltrating distant tissues. The thesis begins in the marrow with a description of (1) nuclear membrane ‘lamina’ physicochemical properties that influence marrow-to-circulation trafficking, and proceeds to detail (2) the physicochemical roles of membrane cortex ‘myosin’ in key marrow processes of motility and division as well as platelet biogenesis and disease. The thesis finishes with (3) studies of macrophages in peripheral tissues far from the marrow and aspects of how such ...